435 research outputs found
PARP1 gene variation and microglial activity on [11C]PBR28 PET in older adults at risk for Alzheimer's disease
Increasing evidence suggests that inflammation is one pathophysio-logical mechanism in Alzheimer's disease (AD). Recent studies have identified an association between the poly (ADP-ribose) polymerase 1 (PARP1) gene and AD. This gene encodes a protein that is involved in many biological functions, including DNA repair and chromatin remodeling, and is a mediator of inflammation. Therefore, we performed a targeted genetic association analysis to investigate the relationship between the PARP1 polymorphisms and brain micro-glial activity as indexed by [11C]PBR28 positron emission tomography (PET). Participants were 26 non-Hispanic Caucasians in the Indiana Memory and Aging Study (IMAS). PET data were intensity-normalized by injected dose/total body weight. Average PBR standardized uptake values (SUV) from 6 bilateral regions of interest (thalamus, frontal, parietal, temporal, and cingulate cortices, and whole brain gray matter) were used as endophenotypes. Single nucleotide polymorphisms (SNPs) with 20% minor allele frequency that were within +/− 20 kb of the PARP1 gene were included in the analyses. Gene-level association analyses were performed using a dominant genetic model with translocator protein (18-kDa) (TSPO) genotype, age at PET scan, and gender as covariates. Analyses were performed with and without APOE ε4 status as a covariate. Associations with PBR SUVs from thalamus and cingulate were significant at corrected p<0.014 and <0.065, respectively. Subsequent multi-marker analysis with cingulate PBR SUV showed that individuals with the “C” allele at rs6677172 and “A” allele at rs61835377 had higher PBR SUV than individuals without these alleles (corrected P<0.03), and individuals with the “G” allele at rs6677172 and “G” allele at rs61835377 displayed the opposite trend (corrected P<0.065). A previous study with the same cohort showed an inverse relationship between PBR SUV and brain atrophy at a follow-up visit, suggesting possible protective effect of microglial activity against cortical atrophy. Interestingly, all 6 AD and 2 of 3 LMCI participants in the current analysis had one or more copies of the “GG” allele combination, associated with lower cingulate PBR SUV, suggesting that this gene variant warrants further investigation
Magnetic field influence on the proximity effect in semiconductor - superconductor hybrid structures and their thermal conductance
We show that a magnetic field can influnce the proximity effect in NS
junctions via diamagnetic screening current flowing in the superconductor.
Using ballistic quasi-one-dimensional (Q1D) electron channels as an example, we
show that the supercurrent flow shifts the proximity-induced minigap in the
excitation spectrum of a Q1D system from the Fermi level to higher
quasiparticle energies. Thermal conductance of a Q1D channel (normalized by
that of a normal Q1D ballistic system) is predicted to manifest such a spectral
feature as a nonmonotonic behavior at temperatures corresponding to the energy
of excitation into the gapful part of the spectrum.Comment: 5 pages, 3 figures, revised version with a new titl
The perseverance of Pacioli's goods inventory accounting system
This paper details sources of the 'undoubtedly strange' (Yamey, 1994a, p.119) system of goods inventory records described in Pacioli’s 1494 bookkeeping treatise and traces the longevity and widespread use of this early perpetual inventory recording (EPIR) system in English language texts. By doing so and contrasting this system with the bookkeeping treatment of modern texts, it is shown that the EPIR system persisted as the dominant form of goods inventory accounting for between 400 and 500 years and that the reasons for its demise are worthy of further consideration and research
HOPX functions as a tumour suppressor in head and neck cancer.
Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis
Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo
We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10 ), MC1R (P = 1.82 × 10 ), a region near TYR (P = 1.57 × 10 ), IFIH1 (P = 4.91 × 10 ), CD80 (P = 3.78 × 10 ), CLNK (P = 1.56 × 10 ), BACH2 (P = 2.53 × 10 ), SLA (P = 1.58 × 10 ), CASP7 (P = 3.56 × 10 ), CD44 (P = 1.78 × 10 ), IKZF4 (P = 2.75 × 10 ), SH2B3 (P = 3.54 × 10 ) and TOB2 (P = 6.81 × 10 ). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
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